Sunday, October 16, 2016

Stem Cell Tourism for Eye Disease: No Passport Required

Stem cell clinics outside the United States, and outside the jurisdiction of the U.S. regulations, have flourished and the pursuit of treatment at these centers has been called “stem cell tourism.” Seekers of unproven stem cell therapies no longer need to look outside the U.S. Paul Knoepfler, a stem cell researcher and leading advocate for the responsible use of stem cell technology, wrote an SBM post on the regulatory aspects of stem cell treatment, a highly recommended read. He also coauthored an article highlighting the direct-to-consumer stem cell industry in the United States. For now, the article is behind a paywall. Fortunately, David Gorski summarized the article here. The authors found a shocking 351 businesses advertising stem cell treatment at 570 locations in the U.S. The problem is that the proliferation of for-profit facilities far outpaces the science on stem cell therapies. Most of these facilities are selling treatments without proven value and with mostly unknown safety.

Clearly, there is no shortage of “experts” prepared to sell you expensive, unproven stem cell treatments for a multitude of diseases. So who can you trust? If I wanted a source of reliable information about stem cell treatment, I might be tempted to seek out the world’s leading homeopathic ophthalmologist!

Introducing: the World’s Leading Homeopathic Ophthalmologist

How do I know Dr. Edward Kondrot is the world’s leading homeopathic ophthalmologist? It says so, right on his website. But it would be an injustice to simply characterize Dr. Kondrot as a homeopathic ophthalmologist. Dr. Kondrot is a Renaissance man of alternative medicine. He is a Board Certified Ophthalmologist, author, radio show host, Fellow of the College of Syntronics, Research Chairman for the College of Syntronics, Adjunct Professor Department of Research at Southwest College of Naturopathic Medicine, President of the Arizona Integrative and Homeopathic Medical Association and member American Academy of Ozonotherapy, just to name a few of the credentials listed on his bio. If you Google Dr. Kondrot’s name you will find he has quite a presence on the internet. I find this video to be particularly endearing.

Dr. Kondrot has recently introduced Stem Cell therapy into his repertoire. According to the website he is using “Cord Stem Cells” trumpeted by the assertion that “the FDA has approved Cord Stem Cells.”

What are cord stem cells?

Blood sequestered in the umbilical cord and placenta of newborn infants contains plasma, red blood cells, white blood cells, platelets and hemopoietic stem cells. Hemopoietic stem cells are capable of differentiating into the various cellular components of blood. These cells are also found in adult bone marrow and to a lesser degree in peripheral blood.

These are the types of cells Dr. Kondrot claims to be using. The use of stem cells derived from umbilical/placental tissue is rather uncommon among rogue stem cell clinics. According to a recent review article, most stem cell clinics use cells derived from the very patient they are treating (autologous cells). Only 3.4% and 0.6% use cells derived from the placenta or umbilical cord, respectively.

Can cord blood treat eye disease?

Despite the lack of any credible data that cord blood can treat anything of the sort, Dr. Kondrot seems to think so. However he provides very few details about what diseases he believes he can treat, or how the treatment is administered.

Did the FDA really approve cord stem cells?

Well, yes, in a limited sense. A single cord blood product has been approved by the Food and Drug Administration (FDA) for a specific set of indications. In 2011 the U.S. FDA approved Hemacord, “an allogenic cord blood hematopoietic progenitor cell therapy…for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system.” In other words, Hemacord is preserved, frozen cord blood, FDA approved for treatment of a variety of conditions in which the body is not producing enough of one or more components of blood. Hemacord is sold by the New York Blood Center.

It is important to understand that FDA approval applies to a specific product for a specific indication or set of indications. The FDA approved Hemacord, a product made from cord blood, and approved it only for a very limited category of conditions. FDA approval does not apply to other sources of stem cells or other indications.

Once a drug is FDA approved, licensed physicians can use their medical judgment to prescribe the drug for an indication that is not explicitly included in the approved indications. This so-called “off-label” use is common practice among ethical physicians practicing evidence-based medicine. The standards are different for research. An approved drug cannot be tested in a research context for an off-label indication without filing appropriate paperwork with the FDA.

Dr. Kondrot interviewed another alternative medicine practitioner, Dennis Courtney, for his Healthy Vision Radio Show. Dr. Courtney has taken over some of the clinical operations at Kondrot’s Healing the Eye & Wellness Center in Florida. A transcript of the interview is posted on Dr. Kondrot’s website. Once they get past congratulating themselves for their individual and collective brilliance, the doctors do reveal a few details about their stem cell practices.

Dr. Courney states that the cells they use come in a 1 milliliter vial, and that each milliliter contains 32 million cells. He further explains that the contents of the 1 milliliter vial are diluted in saline solution and given intravenously. Neither Dr. Kondrot nor Dr. Courtney reveal the source of what they are calling “stem cells.”

Mystery solved

An email to Dr. Kondrot’s office received a prompt reply from one of his assistants identifying the source as a company called Burst Biologics. The company’s website is very heavy on fancy words and pictures of men in lab coats, but very light on content about what their products are and how they should be used. Only two of the products seemed like candidates for what Drs. Kondrot and Courtney are using: BioBurst Fluid and BioBurst Rejuv. The description of each product includes the verbiage: “a cellular allograft with cytokines and growth factors” but they provide no information on the origins of the components. They give no clues or suggestions about how these products might be used.

I called Burst Biologics and spoke with one of their representatives. He explained that BioBurst and BioBurst Rejuv are both derived from cord blood. Red blood cells and some other components of whole blood are removed. He explained that the two products are very similar, but he did not elaborate on the similarities and differences.

I asked if these products were FDA approved. He said their products were in the category of “minimally manipulated” and therefore not subject to FDA regulation as drugs.

The Code of Federal Regulations (CFR) defines the rules for medical use of Human Cell and Tissue Products (HCT/Ps). The FDA has the responsibility for enforcing those rules. Under certain conditions HCT/Ps are viewed as drugs, requiring a complex set of hurdles to define the safety, efficacy, and manufacturing standards before a product can be sold and prescribed. There are certain criteria, however, that exempt HCT/Ps from this level of scrutiny by the FDA. One criterion is “minimal manipulation.” Another is “homologous use”, which means that the product serves a very similar function in the recipient as it did in the donor from which it was derived.

The gray-market in stem cells

The meanings of terms like “minimal manipulation” and “homologous use” are so vague that it is easy for providers to declare their activities as falling into one or more of these categories. This is the regulatory gray area in which many stem cell for-profit centers operate.

The FDA has tried to further clarify the meanings of minimal manipulation, but has rarely taken action in challenging the exemptions claimed by stem cell providers. Dr. Knoepfler has been critical of the FDA’s inaction in confronting the self-serving interpretation of the regulations adopted by the for-profit stem cell industry.

According to Burst Biologic’s description, BioBurst and BioBurst Rejuv clearly fall into the category of HCT/P. They are selling these products under the assumption that the products are exempt from full regulatory scrutiny by the FDA.

Is blood taken from newborn umbilical and placental tissue, then depleted of red blood cells and frozen, really minimally manipulated? If that product is given to adults for treatment of a variety of undefined eye conditions, is that really homologous use? Ultimately it is up to the FDA to decide.

In comparison, consider Hemacord. Hemacord is whole umbilical blood, preserved and frozen. It is prescribed for treatment of conditions in which the recipient is not producing sufficient quantities of cellular blood products. This seems much closer to the definitions of “minimal manipulation” and “homologous use” than BioBurst products for treatment of eye diseases; yet Hemcord is FDA approved and BioBurst is not.

When Dr. Kondrot trumpets the fact that Cord Stem Cells are FDA approved he does not mention that there is no FDA approved stem cell product for treating any eye disease, or that he is using a product that is not FDA approved for treating any disease whatsoever.

Is cord blood treatment safe?

Here is where it gets really scary. Dr. Courtney, in his interview with Dr. Kondrot, had this to say about the safety of stem cell treatment provided at the Healing the Eye and Wellness Center:

We can’t harm you with stem cells. These cells are of such a level of age that they cannot differentiate to any harmful cells. They can’t become a cancer, for instance. That can’t be done with the kind of cells we use. We can only do good. We cannot harm.

Such an absolute, unambiguous endorsement of the safety of intravenous cord blood therapy! Let’s see what the FDA and the Blood Center of New York have to say.

According to the prescribing information for Hemacord, the only FDA approved blood product derived from umbilical and placental tissue, there are serious safety concerns with the use of cord blood.

Hemacord prescribing information comes with a “Black Box” warning. This is the strongest warning that the FDA can require for a prescription medication, and indicates a significant risk of serious or fatal adverse effects. The warning for Hemacord looks like this:

In addition to the Black Box warning, the following potential adverse effects are also on the label:

Malignancies of donor origin

Patients may develop a post-transplant lymphoproliferative disease (PTLD), a potentially fatal disease that behaves like lymphoma. Leukemias of donor origin have also been reported.

Transmission of serious infections

Although donors are carefully screened, transplantation of live human tissue always carries the risk of transmitting serious or even fatal infections.

Transmission of rare genetic diseases

Because the donors are so young (newborns), they may carry genetic diseases not yet evident.

The experts at the New York Blood Center and the FDA have reviewed the data from clinical trials and have enumerated a number of serious and potentially fatal reactions.

Drs. Kondrot and Courtney are administering intravenously a cord blood-derived product that is not FDA approved for any indication. Dr. Courtney has asserted that “we can’t harm you with stem cells.” If the product does indeed contain living human cells (as the seller, and the doctors claim) I see no reason to believe it is intrinsically safer than an FDA approved product containing similar cells. Yes, they are giving a much smaller dose than used for Hemacord. Yes, they may be treating a healthier group of patients. But, given the safety profile for Hemacord, and the lack of rigorously collected safety data for the product they are using, it seems downright reckless to be as cavalier as Dr. Courtney about the safety of stem cell treatment provided at the Healing the Eye and Wellness Center.

Voices of reason

Personally, I trust the judgement of stem cell scientists over homeopathic ophthalmologists. According to Turner and Knoepfler:

There are related ethical concerns about information provided to prospective clients and the veracity of marketing claims, the safety and efficacy of advertised procedures, and the risk of physical, emotional, and financial harm to already ill or injured and vulnerable individuals…The best way to address ethical, legal, and scientific issues related to such businesses is to acknowledge their existence, examine and evaluate their marketing claims, and conduct public debates and policy discussions in the most evidence-based manner possible.